Gao Liyang, Chen Bing, Li Jinhong, Yang Fan, Cen Xuecheng, Liao Zhuangbing, Long Xiao'ao
School of Life Science, Ningxia University, Yinchuan, China.
Stem Cell Research and Cellular Therapy Center, Affiliated Hosptial of Guangdong Medical University, Zhanjiang, China.
PLoS One. 2017 Aug 24;12(8):e0181346. doi: 10.1371/journal.pone.0181346. eCollection 2017.
The Wnt signaling pathway is necessary for the development of the central nervous system and is associated with tumorigenesis in various cancers. However, the mechanism of the Wnt signaling pathway in glioma cells has yet to be elucidated. Small-molecule Wnt modulators such as ICG-001 and AZD2858 were used to inhibit and stimulate the Wnt/β-catenin signaling pathway. Techniques including cell proliferation assay, colony formation assay, Matrigel cell invasion assay, cell cycle assay and Genechip microarray were used. Gene Ontology Enrichment Analysis and Gene Set Enrichment Analysis have enriched many biological processes and signaling pathways. Both the inhibiting and stimulating Wnt/β-catenin signaling pathways could influence the cell cycle, moreover, reduce the proliferation and survival of U87 glioma cells. However, Affymetrix expression microarray indicated that biological processes and networks of signaling pathways between stimulating and inhibiting the Wnt/β-catenin signaling pathway largely differ. We propose that Wnt/β-catenin signaling pathway might prove to be a valuable therapeutic target for glioma.
Wnt信号通路对于中枢神经系统的发育是必需的,并且与多种癌症的肿瘤发生相关。然而,Wnt信号通路在胶质瘤细胞中的机制尚未阐明。使用小分子Wnt调节剂如ICG-001和AZD2858来抑制和刺激Wnt/β-连环蛋白信号通路。采用了包括细胞增殖测定、集落形成测定、基质胶细胞侵袭测定、细胞周期测定和基因芯片微阵列等技术。基因本体富集分析和基因集富集分析丰富了许多生物学过程和信号通路。抑制和刺激Wnt/β-连环蛋白信号通路均可影响细胞周期,此外,还可降低U87胶质瘤细胞的增殖和存活率。然而,Affymetrix表达微阵列表明,刺激和抑制Wnt/β-连环蛋白信号通路之间的生物学过程和信号通路网络存在很大差异。我们认为,Wnt/β-连环蛋白信号通路可能被证明是胶质瘤的一个有价值的治疗靶点。